So, people argue vigorously about the definition of life. They ask if it should have reproduction in it, or metabolism, or evolution. And I don't know the answer to that, so I'm not going to tell you. I will say that life involves computation. So this is a computer program. Booted up in a cell, the program would execute, and it could result in this person; or with a small change, it could result in this person; or another small change, this person; or with a larger change, this dog, or this tree, or this whale.
Oamenii au pareri foarte diferite asupra definitiei vietii. Se intreaba daca ar trebui sa includa reproductie, metabolism, sau evolutie. Eu nu stiu raspunsul, deci nu vi-l pot spune. Sustin insa ca viata presupune calcule. Acesta este un program de calculator. Implementat intr-o celula, programul s-ar executa si ar putea produce aceasta persoana, ori cu o mica schimbare ar putea rezulta in aceasta persoana -- sau cu o alta mica modificare --- aceasta persoana, cu o modificare mai mare, acest caine sau acest copac, ori aceasta balena.
So now, if you take this metaphor [of] genome as program seriously, you have to consider that Chris Anderson is a computer-fabricated artifact, as is Jim Watson, Craig Venter, as are all of us. And in convincing yourself that this metaphor is true, there are lots of similarities between genetic programs and computer programs that could help to convince you. But one, to me, that's most compelling is the peculiar sensitivity to small changes that can make large changes in biological development -- the output. A small mutation can take a two-wing fly and make it a four-wing fly. Or it could take a fly and put legs where its antennae should be. Or if you're familiar with "The Princess Bride," it could create a six-fingered man.
Daca iei in serios aceasta metafora de a privi genomul ca pe un program, trebuie sa admiti ca Chris Anderson e un artefact fabricat de computer, la fel si Jim Watson, Craig Venter, si noi toti. Si ca sa va convingeti ca aceasta metafora este adevarata, considerati numeroasele similaritati intre programele genetice si cele de calculator. Pentru mine cea mai convingatoare e sensibilitatea specifica la variaţii minore care atrag schimbari majore in dezvoltarea biologica finala. O mutatie minora poate transforma o musca cu doua aripi intr-una cu patru aripi. Ori ar putea pune picioruse in locul antenelor. Sau daca ti-e cunoscuta povestea "The Princess Bride" ar putea crea un om cu sase degete.
Now, a hallmark of computer programs is just this kind of sensitivity to small changes. If your bank account's one dollar, and you flip a single bit, you could end up with a thousand dollars. So these small changes are things that I think that -- they indicate to us that a complicated computation in development is underlying these amplified, large changes.
Ei bine, o caracteristica a programelor de calculator este chiar acest tip de sensibilitate la variatii mici. Daca ai intr-un cont bancar $1 si modifici un singur bit te poti trezi cu $1.000. Deci, faptul ca mutatii minore produc modificari amplificate indica prezenta unui proces complex de procesare.
So now, all of this indicates that there are molecular programs underlying biology, and it shows the power of molecular programs -- biology does. And what I want to do is write molecular programs, potentially to build technology. And there are a lot of people doing this, a lot of synthetic biologists doing this, like Craig Venter. And they concentrate on using cells. They're cell-oriented. So my friends, molecular programmers, and I have a sort of biomolecule-centric approach. We're interested in using DNA, RNA and protein, and building new languages for building things from the bottom up, using biomolecules, potentially having nothing to do with biology. So, these are all the machines in a cell. There's a camera. There's the solar panels of the cell, some switches that turn your genes on and off, the girders of the cell, motors that move your muscles. My little group of molecular programmers are trying to refashion all of these parts from DNA. We're not DNA zealots, but DNA is the cheapest, easiest to understand and easy to program material to do this. And as other things become easier to use -- maybe protein -- we'll work with those.
Toate acestea demonstreaza ca exista programe moleculare la baza biologiei a caror putere ne-o demonstreaza biologia. Si ce vreau eu sa fac e sa scriu programe moleculare cu potential in dezvoltarea de tehnologie. Exista o multime de oameni care fac acest lucru, o multime de biologi de sinteza cum e Craig Venter, care insa se concentreaza pe utilizarea intregii celule. Ei se focalizeaza pe celula in intregime. Dar eu si prietenii mei, programatori moleculari, avem o abordare cu pornire de la bio-molecule. Suntem interesati in utilizarea de ADN, ARN si proteine si in implementarea de noi limbi de programare pentru construirea de jos in sus, folosind bio-molecule, cu posibilitatea de a nu avea nimic de-a face cu biologia. Acestea sunt toate mecanismele dintr-o celula. Exista un aparat de fotografiat. Exista panourile solare ale celulei, intrerupatoare care aprind sau sting genele, grinzi ale celulei, motoare care misca muschii. Echipa mea de programatori moleculari incearca sa refasoneze toate aceste parti folosind ADN. Nu suntem fanatici ai ADN-ului, dar ADN-ul e cel mai ieftin, cel mai usor de inteles si e un material simplu de programat. Si pe masura ce alte lucruri devin mai usor de utilizat -- poate proteine -- vom lucra cu acelea în viitor.
If we succeed, what will molecular programming look like? You're going to sit in front of your computer. You're going to design something like a cell phone, and in a high-level language, you'll describe that cell phone. Then you're going to have a compiler that's going to take that description and it's going to turn it into actual molecules that can be sent to a synthesizer and that synthesizer will pack those molecules into a seed. And what happens if you water and feed that seed appropriately, is it will do a developmental computation, a molecular computation, and it'll build an electronic computer. And if I haven't revealed my prejudices already, I think that life has been about molecular computers building electrochemical computers, building electronic computers, which together with electrochemical computers will build new molecular computers, which will build new electronic computers, and so forth.
Si daca reusim, in ce va consta programarea moleculara? Veti sta in fata calculatorului. Veti concepe ceva de genul unui telefon mobil si, intr-un limbaj de nivel inalt, veti descrie acel telefon mobil. Apoi veti avea un compilator care va implementa acest program de descriere si-l va transforma in bio-molecule reale, care pot fi trimise la un sintetizator unde moleculele vor fi impachetate intr-o samanta. Si ce se intampla daca uzi si hranesti acea samanta cum trebuie, este ca va face un calcul de dezvoltare, un calcul molecular, si va construi un computer electronic. Si daca nu mi-am dat inca de gol prejudecatile consider ca viata se poate reduce la computere moleculare care construiesc computere electrochimice care construiesc computere electronice care impreuna cu computerele electrochimice vor construi computere moleculare noi care vor construi noi computere electronice si asa mai departe.
And if you buy all of this, and you think life is about computation, as I do, then you look at big questions through the eyes of a computer scientist. So one big question is, how does a baby know when to stop growing? And for molecular programming, the question is how does your cell phone know when to stop growing? (Laughter) Or how does a computer program know when to stop running? Or more to the point, how do you know if a program will ever stop? There are other questions like this, too. One of them is Craig Venter's question. Turns out I think he's actually a computer scientist. He asked, how big is the minimal genome that will give me a functioning microorganism? How few genes can I use? This is exactly analogous to the question, what's the smallest program I can write that will act exactly like Microsoft Word? (Laughter) And just as he's writing, you know, bacteria that will be smaller, he's writing genomes that will work, we could write smaller programs that would do what Microsoft Word does.
Si daca esti de acord cu toate astea, si crezi ca viata e in intregime calcul, asa cum fac eu, atunci privesti intrebarile vitale prin ochii unui programator. Deci o intrebare importanta e, cum ştie copilul cand sa nu mai creasca? Pentru un programator molecular, intrebarea e: cum stie telefonul tau cand sa se opreasca din creştere? (Rasete) Sau cum stie un program de calculator cand sa se opreasca? Ori si mai concret, cum stim daca se va opri vreodata? Mai exista si alt gen de intrebari. Una dintre ele e intrebarea lui Craig Venter. De fapt se pare ca el gandeste ca un programator. El a intrebat cat de mare trebuie sa fie genomul minim care ar genera un microorganism funcţional. Cat de putine gene pot folosi? Asta e similara cu intrebarea care-i cel mai mic program pe care-l pot scrie care sa opereze exact ca Microsoft Word ? (Rasete) Si la fel cum el concepe, stiti, bacterii care vor fi mai mici, concepe genomuri care vor functiona, noi am putea scrie programe mai mici care sa functioneze ca Microsoft Word.
But for molecular programming, our question is, how many molecules do we need to put in that seed to get a cell phone? What's the smallest number we can get away with? Now, these are big questions in computer science. These are all complexity questions, and computer science tells us that these are very hard questions. Almost -- many of them are impossible. But for some tasks, we can start to answer them. So, I'm going to start asking those questions for the DNA structures I'm going to talk about next. So, this is normal DNA, what you think of as normal DNA. It's double-stranded, it's a double helix, has the As, Ts, Cs and Gs that pair to hold the strands together. And I'm going to draw it like this sometimes, just so I don't scare you. We want to look at individual strands and not think about the double helix. When we synthesize it, it comes single-stranded, so we can take the blue strand in one tube and make an orange strand in the other tube, and they're floppy when they're single-stranded. You mix them together and they make a rigid double helix. Now for the last 25 years, Ned Seeman and a bunch of his descendants have worked very hard and made beautiful three-dimensional structures using this kind of reaction of DNA strands coming together. But a lot of their approaches, though elegant, take a long time. They can take a couple of years, or it can be difficult to design.
Insa in cazul programarii moleculare, intrebarea devine cate molecule trebuie sa impachetam intr-o samanta pentru a obtine un celular. Care-i cel mai mic numar cu care ne-am putea descurca? Acestea sunt intrebari complexe, iar stiinta calculatoarelor confirma ca acestea sunt intrebari foarte grele. Multe dintre ele par intrebari imposibile. Dar pentru unele din ele putem incepe sa raspundem. Deci, voi incepe sa pun acele intrebari pentru structurile ADN de care voi vorbi in continuare. Acesta este ADN-ul normal. E un helix cu catena dubla, in care bazele A, T, C si G se cupleaza pentru a sustine helixul. Si il voi desena uneori liniar, simplificat ca sa nu va sperii. Vrem sa ne uitam la catene singulare si nu la helixul dublu. Cand il sintetizam il obtinem sub forma mono-catenara, astfel incat putem sintetiza lantul albastru intr-un tub si lantul portocaliu in alt tub. Lanturile ADN cand sunt mono-catenare sunt flexibile. Doar cand le amesteci se cupleaza intr-un helix dublu rigid. Ei bine, in ultimii 25 de ani, Ned Seeman si multi din urmasii lui au lucrat din greu si au realizat frumoase structuri tridimensionale folosind acest tip de reactie de cuplare a secventelor monocatenare de ADN. Dar multe din metodele lor, desi elegante, sunt laborioase. Pot dura si doi ani iar design-ul poate fi dificil de programat.
So I came up with a new method a couple of years ago I call DNA origami that's so easy you could do it at home in your kitchen and design the stuff on a laptop. But to do it, you need a long, single strand of DNA, which is technically very difficult to get. So, you can go to a natural source. You can look in this computer-fabricated artifact, and he's got a double-stranded genome -- that's no good. You look in his intestines. There are billions of bacteria. They're no good either. Double strand again, but inside them, they're infected with a virus that has a nice, long, single-stranded genome that we can fold like a piece of paper. And here's how we do it.
Asa ca acum doi ani am inventat o metoda noua, o numesc ADN-origami, care-i atat de simpla ca ati putea-o folosi acasa, in bucatarie si-ati putea programa totul pe un laptop. Dar pentru asta aveti nevoie de un lant lung monocatenar de ADN, care e, tehnic vorbind, foarte dificil de obtinut. In schimb, poti cauta o sursa naturala. Te poti uita la acest artefact fabricat-de-computer dar este dublu-catenar asa ca nu ne e folositor. Te poti uita in intestinele lui. Sunt miliarde de bacterii. Nici astea nu sunt bune. Din nou dublu-catenare, dar in interior sunt infectate cu un virus al carui genom e un frumos lant lung de ADN-singular pe care-l putem impaturi ca pe o bucata de hartie. Si iata cum facem.
This is part of that genome. We add a bunch of short, synthetic DNAs that I call staples. Each one has a left half that binds the long strand in one place, and a right half that binds it in a different place, and brings the long strand together like this. The net action of many of these on that long strand is to fold it into something like a rectangle.
Acesta e o parte din acel genom. Adaugam o gramada de ADN-uri sintetice scurte, pe care le numesc capse. Jumatatea stanga a fiecarei capse se leaga de catena lunga intr-un loc si jumatatea dreapta se leaga intr-un loc diferit si impatureste firul lung de ADN singular asa. Efectul final al multor capse asupra acelei monocatene lungi este o impaturire asemanatoare unui dreptunghi.
Now, we can't actually take a movie of this process, but Shawn Douglas at Harvard has made a nice visualization for us that begins with a long strand and has some short strands in it. And what happens is that we mix these strands together. We heat them up, we add a little bit of salt, we heat them up to almost boiling and cool them down, and as we cool them down, the short strands bind the long strands and start to form structure. And you can see a little bit of double helix forming there. When you look at DNA origami, you can see that what it really is, even though you think it's complicated, is a bunch of double helices that are parallel to each other, and they're held together by places where short strands go along one helix and then jump to another one. So there's a strand that goes like this, goes along one helix and binds -- it jumps to another helix and comes back. That holds the long strand like this.
Din pacate nu putem filma acest proces efectiv, dar Shawn Douglas la Harvard ne-a facut o frumoasa vizualizare virtuala, care incepe cu un lant ADN lung si are cateva catene scurte. Apoi aceste catene lungi si scurte se amesteca impreuna. Le incalzim, adaugam un pic de sare, le incalzim pana aproape de fierbere si apoi le racim. In timp ce se racesc, capsele scurte se prind de catena lunga si incep sa formeze structura; si vedeti cum incepe sa se formeze un helix dublu acolo. Cand te uiti la acest ADN-origami, poti vedea ce este in realitate, si chiar daca pare complicat, nu-i decat o gramada de helixuri duble paralele între ele, care sunt legate de coturi unde unele capse scurte se leaga de o spirala si apoi sar la alta. Iata o capsa care merge de-a lungul unei spirale si apoi sare la un alt helix si face un cot in forma de U, si tine lantul lung de ADN asa.
Now, to show that we could make any shape or pattern that we wanted, I tried to make this shape. I wanted to fold DNA into something that goes up over the eye, down the nose, up the nose, around the forehead, back down and end in a little loop like this. And so, I thought, if this could work, anything could work. So I had the computer program design the short staples to do this. I ordered them; they came by FedEx. I mixed them up, heated them, cooled them down, and I got 50 billion little smiley faces floating around in a single drop of water. And each one of these is just one-thousandth the width of a human hair, OK?
Pentru a demonstra ca putem asambla orice forma sau model dorim, am incercat sa asamblez forma asta. Am vrut sa impaturesc ADN-ul in ceva care se infasoara in jurul ochiului, nasului, in jurul fruntii, inapoi in jos si se incheie intr-o mica bucla. M-am gandit ca daca aceasta forma se poate programa, orice altceva se poate. Deci cu ajutorul computerului am programat capsele necesare pentru a face asta. Le-am comandat, au venit prin FedEx. Le-am amestecat, le-am incalzit, le-am racit, si am obtinut 50 miliarde de ‘feţe zâmbitoare’ microscopice plutind toate intr-o singura picatura de apa. Fiecare dintre acestea este doar o miime din latimea unui fir de par uman, bine?
So, they're all floating around in solution, and to look at them, you have to get them on a surface where they stick. So, you pour them out onto a surface and they start to stick to that surface, and we take a picture using an atomic-force microscope. It's got a needle, like a record needle, that goes back and forth over the surface, bumps up and down, and feels the height of the first surface. It feels the DNA origami. There's the atomic-force microscope working and you can see that the landing's a little rough. When you zoom in, they've got, you know, weak jaws that flip over their heads and some of their noses get punched out, but it's pretty good. You can zoom in and even see the extra little loop, this little nano-goatee.
Deci, toate plutesc in solutie si pentru a te uita la ele, trebuie aduse pe o suprafata uscata de care sa se lipeasca. Le torni pe o suprafaţa, ele incep sa se prinda pe acea suprafata, si facem o poza folosind un microscop de forta atomica (AFM). Acesta are un ac, ca un ac de inregistrat, care merge inainte si inapoi, pe deasupra suprafetei, gliseaza in sus si in jos si apreciaza inaltimea suprafetei. 'Simte' ADN-ul origami. Iata microscopul atomic la lucru, puteti vedea ca aterizarea e putin cam dura. Cand focalizam, au, dupa cum vedeti, unele maxilare sparte si rasucite deasupra capetelor, iar unele dintre nasuri sunt busite, dar in general e destul de bine. Puteti focaliza si vedea chiar mica bucla, acest nano-cioculet mititel.
Now, what's great about this is anybody can do this. And so, I got this in the mail about a year after I did this, unsolicited. Anyone know what this is? What is it? It's China, right? So, what happened is, a graduate student in China, Lulu Qian, did a great job. She wrote all her own software to design and built this DNA origami, a beautiful rendition of China, which even has Taiwan, and you can see it's sort of on the world's shortest leash, right? (Laughter) So, this works really well and you can make patterns as well as shapes, OK? And you can make a map of the Americas and spell DNA with DNA.
Ce-i grozav la acest procedeu este ca oricine poate face asta. Si deci am primit asta in posta cam la un an dupa ce-am facut asta, nesolicitat. Stie cineva ce este asta? Ce este? E harta Chinei, nu-i asa? Deci, ce s-a intamplat este ca o studenta din China, Lulu Qian, a facut o treaba grozava. Si-a programat propriul ei software ca sa proiecteze si sa asambleze acest origami ADN, o frumoasa reprezentare a Chinei, care are chiar si Taiwan-ul, dupa cum vedeti legat prin cea mai scurta lesa din lume, corect? (Rasete) Deci, asta functioneaza foarte bine, poti construi diferite modele si forme. Poti face o harta a Americilor si poti scrie literele ADN folosind ADN.
And what's really neat about it -- well, actually, this all looks like nano-artwork, but it turns out that nano-artwork is just what you need to make nano-circuits. So, you can put circuit components on the staples, like a light bulb and a light switch. Let the thing assemble, and you'll get some kind of a circuit. And then you can maybe wash the DNA away and have the circuit left over. So, this is what some colleagues of mine at Caltech did. They took a DNA origami, organized some carbon nano-tubes, made a little switch, you see here, wired it up, tested it and showed that it is indeed a switch. Now, this is just a single switch and you need half a billion for a computer, so we have a long way to go. But this is very promising because the origami can organize parts just one-tenth the size of those in a normal computer. So it's very promising for making small computers.
Si ce este cu adevarat elegant – e ca toate astea arata ca o nano-opera-de-arta, dar se pare ca nano-operele-de-arta sunt exact ce ai nevoie pentru a face nano-circuite. Deci, poti atasa componente de circuit pe capse, cum ar fi un bec electric si un intrerupator. Lasa-le sa se asambleze si vei obtine un fel de circuit. Si apoi poti spala ADN-ul remanent si ce ramane e circuitul. Exact asta au facut niste colegi de-ai mei de la Caltech. Au luat un origami ADN, au organizat niste nano-tuburi de carbon, au facut un mic comutator, l-au legat, l-au testat si au aratat ca este intr-adevar un comutator. Ei bine, acesta e doar un singur comutator si e nevoie de o jumatate de miliard pentru un computer, deci avem mult de mers. Dar e foarte promitator, intrucat cu origami se pot organiza piese de doar o zecime din dimensiunea celor dintr-un computer normal. Deci, metoda e foarte promitatoare pentru a face computere mici.
Now, I want to get back to that compiler. The DNA origami is a proof that that compiler actually works. So, you start with something in the computer. You get a high-level description of the computer program, a high-level description of the origami. You can compile it to molecules, send it to a synthesizer, and it actually works. And it turns out that a company has made a nice program that's much better than my code, which was kind of ugly, and will allow us to do this in a nice, visual, computer-aided design way.
Acum, vreau sa ma intorc la compilator. ADN-origami este o dovada ca de fapt compilatorul functioneaza. Deci, se incepe cu programul in calculator. Se obtine o descriere in limbaj de programare de înalt nivel, o descriere a acestui origami. Poti sa-l compilezi si sa obtii astfel moleculele, sa le trimiţi la un sintetizator si chiar functioneaza. Si se pare ca o companie a facut un program frumos, care e mult mai bun decat codul meu, care era cam urat, care ne va permite sa facem intr-un mod elegant acest gen de design asistat de calculator.
So, now you can say, all right, why isn't DNA origami the end of the story? You have your molecular compiler, you can do whatever you want. The fact is that it does not scale. So if you want to build a human from DNA origami, the problem is, you need a long strand that's 10 trillion trillion bases long. That's three light years' worth of DNA, so we're not going to do this. We're going to turn to another technology, called algorithmic self-assembly of tiles. It was started by Erik Winfree, and what it does, it has tiles that are a hundredth the size of a DNA origami. You zoom in, there are just four DNA strands and they have little single-stranded bits on them that can bind to other tiles, if they match. And we like to draw these tiles as little squares. And if you look at their sticky ends, these little DNA bits, you can see that they actually form a checkerboard pattern. So, these tiles would make a complicated, self-assembling checkerboard. And the point of this, if you didn't catch that, is that tiles are a kind of molecular program and they can output patterns. And a really amazing part of this is that any computer program can be translated into one of these tile programs -- specifically, counting. So, you can come up with a set of tiles that when they come together, form a little binary counter rather than a checkerboard. So you can read off binary numbers five, six and seven.
Deci, acum ai putea intreba, bine, de ce nu este ADN-origami sfarsitul povestii ? Ai compilatorul molecular, poti programa orice vrei. In realitate metoda nu se aplica bine la scara mare. Daca vrei sa construiesti un om din ADN-origami, problema e ca trebuie sa pornesti de la un lant lung de 10 trilioane de trilioane de baze. Asta-i egal cu trei ani lumina de ADN, deci nu vom face asta. In schimb vom considera o alta tehnologie numita auto-asamblare algoritmica de dale. Tehnologia a fost initiata de Erik Winfree, si ce face ea, are dale care sunt a suta parte din marimea unui ADN-origami. Fiecare placuta e alcatuita din patru secvente de ADN si acestea au bucatele mono-catenate pe ele care se pot lipi de alte dale daca se potrivesc. Pentru simplificare reprezentam aceste dale ca patratele. Daca te uiti la capetele lipicioase ale acestor bucatele de ADN vezi ca formeaza de fapt o structura ca tabla de sah. Deci, aceste placi se auto-asambleaza intr-o tabla de sah complicata. Esentialul este, in caz ca nu v-ati dat seama, ca aceste placute asamblate sunt un fel de program molecular care poate crea modele. Si o parte cu adevarat uimitoare a acestui fapt e ca orice program de calculator poate fi tradus intr-un astfel de program de placute ADN -- cum ar fi un algoritm de numarare. Deci, puteti asambla un set de placute ADN care alcatuiesc mai degraba un mic sistem de numaratoare binara decat o tabla de sah. Astfel puteti citi numere binare, cinci, şase şi şapte.
And in order to get these kinds of computations started right, you need some kind of input, a kind of seed. You can use DNA origami for that. You can encode the number 32 in the right-hand side of a DNA origami, and when you add those tiles that count, they will start to count -- they will read that 32 and they'll stop at 32. So, what we've done is we've figured out a way to have a molecular program know when to stop going. It knows when to stop growing because it can count. It knows how big it is. So, that answers that sort of first question I was talking about. It doesn't tell us how babies do it, however.
Ca sa pornim corect acest gen de calcule, avem nevoie de date de intrare, un fel de samanta. Putem folosi ADN-origami pentru asta. Codificam numarul 32 in partea dreapta a unui ADN-origami si cand adaugam acele placute care numara ele vor incepe sa numere, sa citeasca acel 32 si se vor opri la 32. Deci, ce am realizat este ca am gasit o metoda de a determina un program molecular sa stie cand sa se opreasca din crestere. Stie cand sa se opreasca din crestere pentru ca stie sa numere. Stie cat este de mare. Prin urmare, asta raspunde la acea prima intrebare pe care am mentionat-o. Nu ne spune insa cum stiu copiii sa se opreasca din crestere.
So now, we can use this counting to try and get at much bigger things than DNA origami could otherwise. Here's the DNA origami, and what we can do is we can write 32 on both edges of the DNA origami, and we can now use our watering can and water with tiles, and we can start growing tiles off of that and create a square. The counter serves as a template to fill in a square in the middle of this thing. So, what we've done is we've succeeded in making something much bigger than a DNA origami by combining DNA origami with tiles. And the neat thing about it is, is that it's also reprogrammable. You can just change a couple of the DNA strands in this binary representation and you'll get 96 rather than 32. And if you do that, the origami's the same size, but the resulting square that you get is three times bigger.
Acum, putem folosi aceasta numarare pentru a asambla sisteme mult mai mari decat am fi putut cu metoda ADN-origami. Aici e o structura ADN-origami, ce putem face, putem scrie cate un 32 la ambele margini ale ADN-ului origami iar apoi folosind stropitoarea si adaugand dale si putem sa initiem o crestere cu ajutorul placutelor si sa cream un patrat. Contorul serveste ca un sablon care umple acest patrat in mijloc. Prin urmare am reusit sa cream ceva de marime mult mai mare decat un ADN origami prin combinarea de ADN-origami cu dale. Si partea frumoasa e ca acestea sunt reprogramabile. Prin schimbarea a doua catene de ADN in aceasta reprezentare binara se obtine o latura de 96 in loc de 32. Si daca faci asta, AND-ul origami e de aceeasi marime, dar patratul final e de trei ori mai mare.
So, this sort of recapitulates what I was telling you about development. You have a very sensitive computer program where small changes -- single, tiny, little mutations -- can take something that made one size square and make something very much bigger. Now, this -- using counting to compute and build these kinds of things by this kind of developmental process is something that also has bearing on Craig Venter's question. So, you can ask, how many DNA strands are required to build a square of a given size? If we wanted to make a square of size 10, 100 or 1,000, if we used DNA origami alone, we would require a number of DNA strands that's the square of the size of that square; so we'd need 100, 10,000 or a million DNA strands. That's really not affordable. But if we use a little computation -- we use origami, plus some tiles that count -- then we can get away with using 100, 200 or 300 DNA strands. And so we can exponentially reduce the number of DNA strands we use, if we use counting, if we use a little bit of computation. And so computation is some very powerful way to reduce the number of molecules you need to build something, to reduce the size of the genome that you're building.
Sa recapitulam acum ce va spuneam depre cresterea programata. Aveti un program de computer foarte sensibil unde schimbari minore -- mutaţii singulare, minore --- pot lua ceva care a facut un patrat de o anumita marime si face o structura mult mai mare. Acum, folosirea acestui gen de algoritm si asamblarea acestui gen de structuri prin acest proces de augmentare ne ajuta sa raspundem si la intrebarea lui Craig Venter. Deci, puteti intreba, cate catene de ADN sunt necesare pentru a construi un patrat de o marime data? Daca am dori sa realizam un patrat de 10, 100 sau 1.000, si daca am folosi doar ADN-origami, ar fi necesar un numar de monocatene de ADN egal cu acea marime la patrat; deci am avea nevoie de 100, 10.000 respectiv 1.000.000 de catene ADN. Nu ne putem permite asta. Dar daca folosim cateva computatii -- adica folosim origami plus placute care numara -- atunci putem scapa folosind un numar de 100, 200, 300 de lanturi. Si astfel putem reduce exponential numarul de catene ADN necesare daca folosim ceva calcule. Prin urmare aceste calcule au potential mare de a reduce numarul de molecule de care ai nevoie ca sa construiesti ceva, de a reduce marimea genomului pe care il asamblezi.
And finally, I'm going to get back to that sort of crazy idea about computers building computers. If you look at the square that you build with the origami and some counters growing off it, the pattern that it has is exactly the pattern that you need to make a memory. So if you affix some wires and switches to those tiles -- rather than to the staple strands, you affix them to the tiles -- then they'll self-assemble the somewhat complicated circuits, the demultiplexer circuits, that you need to address this memory. So you can actually make a complicated circuit using a little bit of computation. It's a molecular computer building an electronic computer. Now, you ask me, how far have we gotten down this path? Experimentally, this is what we've done in the last year. Here is a DNA origami rectangle, and here are some tiles growing from it. And you can see how they count. One, two, three, four, five, six, nine, 10, 11, 12, 17. So it's got some errors, but at least it counts up. (Laughter)
Si in sfarsit, ma voi referi din nou la acea idee indrazneata respectiv computere care construiesc computere. Daca va uitati la patratul construit cu origami si la numaratorile care rezulta din acestea tiparul pe care il are este exact cel de care ai nevoie pentru a crea o memorie. Acum, daca aplici niste conexiuni si intrerupatoare la acele dale, in loc sa le aplici pe capse atunci se pot auto-asambla circuite destul de complicate --- circuite de-multiplexer necesare pentru a adresa memoria unui calculator. In concluzie chiar putem construi circuite complicate folosind putina computatie. Aici avem un computer molecular care construieste un computer electronic. Poate va intrebati cat de departe am ajuns in aceasta directie. Experimental, iata ce am facut anul trecut. Acesta e un dreptunghi de ADN-origami, iar aici sunt niste placute care au crescut din el. Si puteti vedea cum calculeaza ele. 1, 2, 3, 4, 5, 6, 9, 10, 11, 12, 17. Observati niste erori, dar cel putin numara in sus. (Rasete)
So, it turns out we actually had this idea nine years ago, and that's about the time constant for how long it takes to do these kinds of things, so I think we made a lot of progress. We've got ideas about how to fix these errors. And I think in the next five or 10 years, we'll make the kind of squares that I described and maybe even get to some of those self-assembled circuits.
De fapt ne-a venit aceasta idee acum noua ani, dar, considerand constanta de timp necesara realizarii efective, consideram ca am progresat mult. Avem ceva idei de cum sa reparam aceste erori. Si cred ca in urmatorii 5 sau 10 ani vom face patratelele pe care le-am descris si poate chiar si acele circuite auto-asamblate.
So now, what do I want you to take away from this talk? I want you to remember that to create life's very diverse and complex forms, life uses computation to do that. And the computations that it uses, they're molecular computations, and in order to understand this and get a better handle on it, as Feynman said, you know, we need to build something to understand it. And so we are going to use molecules and refashion this thing, rebuild everything from the bottom up, using DNA in ways that nature never intended, using DNA origami, and DNA origami to seed this algorithmic self-assembly.
In concluzie, cu ce as dori sa ramaneti din aceasta prezentare? As dori sa retineti ca pentru a crea formele diverse si complexe de viata viata foloseste calcule in acest scop. Aceste calcule sunt computatii moleculare iar in scopul de a le intelege mai bine cum spunea Feyman, trebuie sa le construim ca sa le intelegem. Si astfel vom folosi molecule ADN si le vom refasona, reconstruind totul de jos in sus, folosind ADN-ul in moduri in care natura nu a intentionat niciodata, folosind ADN-origami, fie ca atare, fie pentru a initia aceste auto-asamblari algoritmice.
You know, so this is all very cool, but what I'd like you to take from the talk, hopefully from some of those big questions, is that this molecular programming isn't just about making gadgets. It's not just making about -- it's making self-assembled cell phones and circuits. What it's really about is taking computer science and looking at big questions in a new light, asking new versions of those big questions and trying to understand how biology can make such amazing things. Thank you. (Applause)
Ei bine, toate acestea sunt grozave, dar ce mi-ar placea sa retineti din prezentare, din acele intrebari majore, este ca aceste programe moleculare nu se reduc doar la a construi dispozitive, doar la asamblarea de celulare si circuite. Ceea ce este cu adevarat important e a reusi in procesul de programare sa privim intrebarile vietii intr-o lumina noua, sa cream versiuni noi ale acelor intrebari complexe si sa incercam sa intelegem cum reuseste biologia sa faca astfel de lucruri uimitoare. Multumesc. (Aplauze)